Kidney transplant outcomes in patients with complement dysregulation

Table 1 Baseline demographic and clinical characteristics of the study cohort, n (%)

Variable	Value
Age (years)
mean ± SD	36.3 ± 9.3
Median (IQR)	33.0 (30.3-43.8)
Range	22-58
Sex
Male	32 (84.2)
Female	6 (15.8)
Hypertension
Present	37 (97.4)
Absent	1 (2.6)
Diabetes status
Diabetes mellitus	1 (2.6)
Post-transplant diabetes mellitus (NODAT)	3 (7.9)
No diabetes	34 (89.5)
Clinical scenario at diagnosis of complement abnormality
CKD stage V on maintenance hemodialysis	28 (73.7)
Advanced CKD stage V not on dialysis	3 (7.9)
AKI	3 (7.9)
Diagnosed post-transplant	4 (10.5)
Median post-transplant follow-up (months)	12
Survival at last follow-up
Alive	36 (94.7)
Deceased	2 (5.3)

AKI: Acute kidney injury; CKD: Chronic kidney disease; IQR: Interquartile range; NODAT: New-onset diabetes after transplantation; SD: Standard deviation.

Table 2 Complement genetic abnormalities in the study cohort

Gene	Duplication	Heterozygous deletion	Homozygous deletion
CFHR1/3	19	8	3
CFHR5	0	2	0
CFH	0	5	2
CFB	0	2	0

Table 3 Anti-factor H antibody positivity

Anti-factor H antibody (≥ 100 AU/mL)	n (%)
Positive	15 (39.5)
Negative	23 (60.5)

Table 4 Distribution of complement genetic abnormalities according to anti-factor H antibody status

Complement genetic abnormality	AFH-positive (n = 15)	AFH-negative (n = 23)	Total n (%)
CFHR1/CFHR3 rearrangements	9	21	30 (78.9)
Duplication	6	13	19
Heterozygous deletion	2	6	8
Homozygous deletion	1	2	3
CFH mutation	3	4	7 (18.4)
Heterozygous mutation	2	3	5
Homozygous mutation	1	1	2
CFHR5 mutation	1	1	2 (5.3)
CFB mutation	1	1	2 (5.3)
No genetic abnormality identified	4	0	4 (10.5)

AFH: Anti-factor H; CFB: Complement factor B; CFH: Complement factor H; CFHR: Complement factor H-related genes.

Table 5 Characteristics of recurrence cohort (n = 7)

Case	Complement genetic abnormality	AFH ≥ 100	Genetic details	Pre-transplant treatment	Post-transplant treatment	Outcome
1	Present	Yes	CFHR1-CFHR3 homozygous deletion	-	5 PE + rituximab (500 × 2)	Functioning graft
2	Present	Yes	CFHR1-CFHR3 duplication	6 PE + rituximab 500 mg	Modified immunosuppression	Functioning graft
3	Present	No	CFH heterozygous + CFHR1/3 duplication	3 PE + rituximab 500 mg	4 PE	Functioning graft
4	Present	No	CFHR1-CFHR3 duplication	5 PE + rituximab 500 mg	3 PE + IVIG + bortezomib	Functioning graft
5	Present	No	CFHR1-CFHR3 duplication	-	PE	Graft loss (history of mucormycosis)
6	Present	No	CFHR1 heterozygous	-	4 PE + rituximab 200 mg	Functioning graft
7	Present	No	CFHR1 heterozygous	-	3 PE + eculizumab	Functioning graft

Numbers preceding plasma exchange indicate the number of plasma exchange sessions administered. Rituximab doses are expressed per administration. AFH: Anti-factor H antibody; CFH: Complement factor H; CFHR: Complement factor H-related protein; IVIG: Intravenous immunoglobulin; PE: Plasma exchange.